Affinage

ALOX5

Polyunsaturated fatty acid 5-lipoxygenase · UniProt P09917

Length
674 aa
Mass
78.0 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALOX5 encodes arachidonate 5-lipoxygenase, the enzyme that oxygenates arachidonic acid at the 5S position to produce 5(S)-HpETE and subsequently leukotrienes (LTB4, LTC4) and 5-HETE, with reaction specificity determined by a triad of residues (Phe359, Ala424, Asn425, Ala603) that define substrate orientation within the active-site pocket (PMID:23246375, PMID:31664810). ALOX5 activity is regulated at multiple levels: transcriptionally through Sp1/Egr1 tandem-repeat promoter elements, KLF6, EGR1, PRC2-mediated repression, and LPS signaling (PMID:10369259, PMID:24130502, PMID:38062004, PMID:28500307, PMID:32120263); post-translationally by PARP-1-mediated PARylation that stabilizes the protein, by Erk1-dependent phosphorylation that drives nuclear membrane translocation, and by FLAP cofactor stabilization (PMID:38172525, PMID:36231015, PMID:36921996); and functionally through stimulus-dependent cytosol-to-nuclear-membrane redistribution (PMID:17484769). Downstream, ALOX5-derived lipid mediators drive leukocyte migration via JNK/c-Jun, promote CD4+ T cell pyroptosis through an LTB4–ORAI3–NLRP3 axis, execute ferroptosis through ACSL4-independent lipid peroxidation and AMPK/mTOR–GPX4 suppression, sustain leukemia stem cell survival in CML and polycythemia vera through AKT/β-catenin signaling, regulate macrophage M2 polarization via JAK/STAT and PI3K pathways, and support pancreatic β-cell insulin secretion (PMID:23539630, PMID:38412254, PMID:36231015, PMID:37080437, PMID:19503090, PMID:27784744, PMID:37348233, PMID:38124204, PMID:18421434).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    The question of how ALOX5 transcription is regulated was addressed by identifying a variable tandem-repeat element of Sp1/Egr1 sites in the core promoter, establishing that copy-number variation at this locus controls enzyme expression and leukotriene output.

    Evidence Promoter-reporter assays in tissue culture combined with pharmacogenetic clinical association in asthma patients

    PMID:10369259

    Open questions at the time
    • Mechanism by which non-5 repeat alleles reduce transcription not fully resolved
    • Identity of chromatin remodeling factors at the tandem-repeat locus unknown
  2. 2000 Medium

    Whether ALOX5 expression and subcellular distribution change with aging was answered by showing increased mRNA/protein and enhanced membrane translocation in aged rat brain, establishing that aging itself upregulates and activates ALOX5.

    Evidence Quantitative RT-PCR, Western blotting, and subcellular fractionation in young versus aged rat hippocampus and cerebellum

    PMID:11016533

    Open questions at the time
    • Causal relationship between membrane translocation and age-related neuroinflammation not tested
    • Human aging tissue not examined
  3. 2006 Medium

    The functional impact of promoter tandem-repeat variation in primary human cells was confirmed by showing that eosinophils homozygous for non-5 repeat alleles produce less ALOX5 mRNA and LTC4, validating the promoter polymorphism as a determinant of leukotriene biosynthetic capacity.

    Evidence RT-PCR and LTC4 ELISA in genotyped primary human eosinophils

    PMID:16364163

    Open questions at the time
    • Sample size limited
    • Whether other cell types show the same quantitative relationship is untested
  4. 2007 Medium

    The question of how ALOX5 is activated in lymphocytes was addressed by demonstrating that the enzyme resides in the cytoplasm of resting T cells and translocates to the nuclear periphery upon mitogenic stimulation, coupling subcellular redistribution to leukotriene synthesis.

    Evidence Immunofluorescence, subcellular fractionation, and leukotriene synthesis assays with pharmacological inhibitors in primary T cells and Jurkat cells

    PMID:17484769

    Open questions at the time
    • Stimulus-specific translocation signals not identified
    • Whether translocation requires FLAP in T cells not tested
  5. 2009 High

    A convergent lipid peroxidation pathway was revealed when 5S-HETE (the ALOX5 product) was shown to be further oxygenated by COX-2 to yield a di-endoperoxide whose heme-catalyzed cleavage generates 4S-HNE and malondialdehyde, connecting ALOX5 to canonical oxidative damage markers.

    Evidence In vitro reconstitution with purified enzymes and heme; HPLC with chiral-phase stereochemical assignment

    PMID:19553698

    Open questions at the time
    • Cellular relevance of this convergent pathway not demonstrated in intact cells
    • Relative contribution versus direct lipid peroxidation unknown
  6. 2009 High

    The long-standing question of whether ALOX5 is dispensable for normal hematopoiesis but essential for leukemia was answered by showing that Alox5 knockout prevents CML development by selectively eliminating leukemia stem cells while sparing normal HSCs.

    Evidence Alox5 knockout mice; BCR-ABL bone marrow transplantation CML model; colony-forming assays; zileuton validation

    PMID:19503090

    Open questions at the time
    • Direct molecular target of ALOX5 products in LSCs not identified at this stage
    • Whether ALOX5 inhibition eradicates established CML not tested
  7. 2011 High

    ALOX5 was established as a regulator of pancreatic β-cell function: Alox5−/− mice show impaired glucose-stimulated insulin secretion and reduced insulin/PDX1 expression, phenocopied by siRNA in human islets, extending ALOX5 biology beyond immunity.

    Evidence Alox5 knockout mice with glucose tolerance tests; isolated islet insulin secretion assays; siRNA in human islets

    PMID:18421434

    Open questions at the time
    • Which specific ALOX5 product mediates β-cell signaling is unknown
    • Downstream signaling pathway linking 5-LO to PDX1 expression not defined
  8. 2012 High

    The structural basis of ALOX5 positional specificity was established by showing that mutagenesis of three triad determinants (Phe359Trp/Ala424Ile/Asn425Met) converts the enzyme from 5S- to dominant 15S-lipoxygenation in both mouse and human orthologs, proving that active-site pocket geometry dictates substrate oxygenation position.

    Evidence Site-directed mutagenesis of recombinant mouse and human ALOX5; HPLC product analysis; structural modeling

    PMID:23246375

    Open questions at the time
    • Crystal structure of mutant enzyme not determined
    • Whether these residues also control LTA4 synthase activity not tested
  9. 2013 High

    ALOX5 was placed in a transcriptional signaling cascade for leukocyte migration: Cnr2 suppresses migration by inhibiting JNK/c-Jun-dependent ALOX5 transcription, while in AML, KLF6 is required for oncogene-driven ALOX5 upregulation, establishing ALOX5 as a convergent transcriptional target of both inflammatory and oncogenic signals.

    Evidence Zinc finger nuclease mutagenesis in zebrafish; chemical epistasis; ChIP for c-Jun and KLF6; validation in human myeloid cells and leukemia models

    PMID:23539630 PMID:24130502

    Open questions at the time
    • Direct c-Jun binding site on ALOX5 promoter not mapped in human cells
    • Whether KLF6 cooperates with Sp1/Egr1 tandem-repeat elements unclear
  10. 2014 Medium

    ALOX5 was identified as a mediator of stress-induced Alzheimer's-like tauopathy: genetic deletion in 3xTg AD mice prevents stress-induced tau hyperphosphorylation, GSK3β activation, LTP impairment, and memory deficits.

    Evidence 3xTg/5LO−/− mice; restraint/isolation stress; LTP electrophysiology; fear conditioning; phospho-tau/GSK3β Western blot

    PMID:25122659

    Open questions at the time
    • Which ALOX5-derived lipid mediator activates GSK3β not identified
    • Not replicated in an independent AD mouse model
    • Human relevance not established
  11. 2016 High

    ALOX5 was shown to mediate JAK2V617F-driven polycythemia vera through AKT activation and β-catenin maintenance, extending the CML finding to a second myeloproliferative neoplasm and defining the downstream effector pathway.

    Evidence JAK2V617F PV mouse model; Alox5 KO and zileuton; colony assays from human JAK2V617F CD34+ cells; AKT/β-catenin Western blot

    PMID:27784744

    Open questions at the time
    • Whether AKT activation is directly mediated by a specific leukotriene receptor is untested
    • Long-term HSC effects of Alox5 loss in PV not studied
  12. 2017 Medium

    PRC2-mediated epigenetic silencing of ALOX5 in MLL-rearranged AML was discovered, showing that ALOX5 can function as a context-dependent tumor suppressor whose restoration sensitizes leukemia cells to chemotherapy.

    Evidence ChIP for PRC2 marks at ALOX5 promoter; colony-forming and bone marrow transplantation assays; drug sensitivity assays

    PMID:28500307

    Open questions at the time
    • Mechanism by which restored ALOX5 sensitizes to doxorubicin/cytarabine is unclear
    • Apparent contradiction with CML/PV role not reconciled mechanistically
  13. 2019 High

    Computational and biochemical dissection of all four triad determinants (including Ala603Ile) confirmed that mutagenesis abolishes both 5S-lipoxygenation and LTA4 synthase activity, with QM/MM modeling showing altered substrate alignment, completing the structural picture of ALOX5 specificity.

    Evidence Recombinant Sf9 expression; HPLC; stereospecifically deuterium-labeled substrates; in silico docking, MD, QM/MM

    PMID:31664810

    Open questions at the time
    • No experimentally determined crystal structure of mutant active site
    • Dynamics of substrate entry into the pocket not characterized
  14. 2020 Medium

    Systematic identification of ALOX5 promoter-binding proteins revealed G-quadruplex structures in the GC-rich promoter and identified novel transcriptional regulators (KLF13, KLF16, MAZ, ZBTB7A) and G-quadruplex interactors (BLM, DHX36), expanding the regulatory landscape beyond Sp1/Egr1.

    Evidence DNA pulldown coupled to label-free quantitative mass spectrometry; circular dichroism spectroscopy; antibody-based G-quadruplex detection

    PMID:32096311

    Open questions at the time
    • Functional validation of individual novel regulators not performed
    • Whether G-quadruplex structures regulate transcription in vivo is unknown
  15. 2021 Medium

    A PKCβ–ERK1/2–ALOX5–PTEN axis was defined as a mechanism of BCR-ABL-independent TKI resistance in CML, showing that ALOX5 inactivates PTEN downstream of ERK signaling to sustain resistance.

    Evidence shRNA knockdown; ERK inhibitors; PTEN activity assays; CML-PDX mouse model with PKCβ inhibitor

    PMID:33561320

    Open questions at the time
    • Direct mechanism of PTEN inactivation by ALOX5 products not identified
    • Single lab without independent replication
  16. 2022 High

    ALOX5 was established as a caspase-9-parallel cell death executor: Erk1-dependent phosphorylation targets ALOX5 to the nuclear membrane where it mediates lipid peroxidation causing DNA damage and cell death; double knockout of caspase-9 and Alox5 causes T cell expansion in vivo, demonstrating non-redundant regulation of T cell homeostasis.

    Evidence Genome-wide siRNA screen; caspase-9/Alox5 double-KO mice; ROS/lipid peroxidation assays; subcellular imaging

    PMID:36231015

    Open questions at the time
    • Identity of specific lipid peroxidation products at the nuclear membrane not determined
    • Whether this pathway operates in non-T cell lineages unknown
  17. 2022 Medium

    ERK-dependent ALOX5 activation was shown to mediate ferroptosis in neurons downstream of lysyl oxidase, linking ALOX5 to seizure-induced hippocampal neuronal death.

    Evidence AAV-based LysOX overexpression; ERK inhibitor studies; lipid peroxidation assays; seizure mouse model

    PMID:36176900

    Open questions at the time
    • Whether ALOX5-mediated neuronal ferroptosis is ACSL4-dependent or independent not clarified
    • Single lab
  18. 2023 High

    ALOX5 was linked to Huntington's disease pathogenesis: polyglutamine-expanded huntingtin stabilizes FLAP, enhancing ALOX5 activity and triggering ferroptosis selectively under HD-relevant stress; Alox5 knockout ameliorates HD pathology and extends lifespan in HD mice.

    Evidence RNAi genome screen; ALOX5–FLAP co-IP and stabilization assays; neuronal ferroptosis assays; Alox5 KO in HD mouse model

    PMID:36921996

    Open questions at the time
    • Mechanism by which mutant huntingtin stabilizes FLAP not fully elucidated
    • Whether ALOX5 inhibition benefits manifest HD not tested
  19. 2023 Medium

    Multiple studies established ALOX5-derived 5-HETE and LTB4 as drivers of immunosuppressive M2 macrophage polarization across cancer types, acting through JAK/STAT in pancreatic cancer, PI3K via BLT1/BLT2 in cholangiocarcinoma, and NRF2 nuclear translocation in glioma, while EGR1-dependent ALOX5 expression was shown to be required for ferroptosis sensitivity in bladder cancer.

    Evidence Lentiviral overexpression; zileuton and receptor-blocking studies; orthotopic and xenograft mouse models; CRISPR/Cas9 KO; ChIP for EGR1; oxylipin profiling

    PMID:37080437 PMID:37348233 PMID:38062004 PMID:38124204 PMID:39142719

    Open questions at the time
    • Whether the M2-promoting and ferroptosis-promoting roles of ALOX5 are context-exclusive or coexist in a single tumor is unresolved
    • Relative contribution of LTB4 versus 5-HETE to immunosuppression not established in a unified system
  20. 2024 High

    A complete LTB4–ORAI3–NLRP3 pyroptosis pathway was delineated in CD4+ T cells from RA patients, showing that ALOX5-derived LTB4 triggers Ca2+ influx through ORAI3, activating NLRP3 inflammasome-mediated pyroptosis, with in vivo validation in two rodent arthritis models.

    Evidence Patient T cell analysis; ALOX5 knockdown; LTB4 ELISA; Ca2+ flux assays; ORAI3 blocking; NLRP3 activation; two rodent RA models

    PMID:38412254

    Open questions at the time
    • Whether this pathway operates in other autoimmune T cell–driven diseases unknown
    • Structural basis of LTB4–ORAI3 interaction not defined
  21. 2024 Medium

    PARP-1 was identified as a post-translational stabilizer of ALOX5 through PARylation, linking DNA damage response signaling to leukotriene biosynthesis in tumor-associated neutrophils.

    Evidence Co-IP/mass spectrometry; PARylation assay; PARP-1 knockdown and inhibitor; murine tumor model

    PMID:38172525

    Open questions at the time
    • PARylation site(s) on ALOX5 not mapped
    • Whether PARylation affects ALOX5 enzymatic activity or only stability not distinguished
    • Not replicated independently

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how ALOX5 functions as a pro-tumorigenic factor in CML/PV while acting as a PRC2-repressed tumor suppressor in MLL-AML; (2) which specific lipid products mediate nuclear-membrane ferroptosis versus conventional leukotriene signaling; (3) the structural basis of FLAP stabilization by mutant huntingtin; and (4) whether ALOX5 promoter G-quadruplex structures regulate transcription in vivo.
  • Context-dependent oncogene vs. tumor suppressor function not mechanistically reconciled
  • No crystal structure of ALOX5–FLAP complex
  • In vivo relevance of G-quadruplex promoter regulation untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0008289 lipid binding 2
Localization
GO:0005634 nucleus 2 GO:0005635 nuclear envelope 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 6 R-HSA-168256 Immune System 5 R-HSA-1430728 Metabolism 4

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The ALOX5 core promoter contains a variable number of Sp1/Egr1-binding tandem repeats; variants with other than five repeats show diminished promoter-reporter activity in tissue culture, leading to reduced ALOX5 transcription and decreased leukotriene production, which predicts differential clinical response to ALOX5-pathway modifiers in asthma. Promoter-reporter (luciferase) assay in tissue culture; pharmacogenetic clinical association study Nature genetics High 10369259
2006 Eosinophils bearing the ALOX5 promoter non5/non5 genotype express less ALOX5 mRNA and produce less LTC4 than those with the 5/5 genotype, directly linking the tandem-repeat polymorphism to reduced enzyme expression and leukotriene output in primary human cells. In vitro eosinophil culture; RT-PCR for ALOX5 mRNA; LTC4 ELISA; genotyping Allergy Medium 16364163
2009 Alox5 is required for BCR-ABL-induced chronic myeloid leukemia (CML) in mice; loss of Alox5 impairs differentiation, cell division, and survival of long-term leukemia stem cells (LT-LSCs) without significantly affecting normal hematopoietic stem cells, preventing CML development. Alox5 knockout mouse model; BCR-ABL bone marrow transplantation CML model; colony-forming and replating assays; flow cytometry for LSC populations; pharmacological inhibition with zileuton Nature genetics High 19503090
2009 The 5-lipoxygenase product 5S-HETE is oxygenated by COX-2 to yield a bicyclic di-endoperoxide; heme (hematin or ferrous iron) catalyzes cleavage of both peroxide O–O bonds to generate 4S-HNE, 8-oxo-5S-hydroxy-6E-octenoic acid, and malondialdehyde, identifying a convergent ALOX5/COX-2 pathway that produces canonical lipid peroxidation products. In vitro enzymatic assay with purified hematin/ferrous chloride; HPLC product analysis; chiral-phase HPLC for stereochemical assignment Journal of lipid research High 19553698
2011 ALOX5 inhibition with zileuton or knockdown of Alox5 expression reduces ALOX5 activity and impairs insulin secretion in pancreatic islets; Alox5-/- mice show increased fat mass, impaired glucose-stimulated insulin secretion, and decreased insulin/PDX1 gene expression; siRNA knockdown of ALOX5 in human islets phenocopies this, demonstrating a direct role for 5-LO in pancreatic beta-cell function. Alox5 knockout mice; in vivo glucose tolerance tests; isolated islet insulin secretion assays; siRNA knockdown in human islets; RT-PCR for insulin and PDX1 Diabetologia High 18421434
2012 Reduction of the substrate-binding pocket volume of mouse Alox5 by multiple mutations (Phe359Trp + Ala424Ile + Asn425Met) converts it from a 5-lipoxygenating enzyme to a dominant 15S-lipoxygenating enzyme; the same triad mutations in human ALOX5 yield the same result, establishing that pocket geometry determines reaction specificity. Site-directed mutagenesis; recombinant enzyme expression; HPLC product analysis; structural modeling Archives of biochemistry and biophysics High 23246375
2013 Cannabinoid receptor 2 (Cnr2) activation suppresses leukocyte inflammatory migration by downregulating Alox5 expression through inhibition of the JNK/c-Jun signaling axis; alox5 is a direct transcriptional target of c-Jun; genetic inactivation of Alox5 blocks leukocyte migration in zebrafish, establishing a Cnr2–JNK–c-Jun–Alox5 pathway. Chemical genetic screen in zebrafish; zinc finger nuclease-mediated Cnr2 and Alox5 mutagenesis; leukocyte migration assays; JNK/c-Jun inhibitor studies; human myeloid cell validation The Journal of biological chemistry High 23539630
2013 RUNX1-ETO9a upregulates Alox5 via the C2H2 zinc finger transcription factor KLF6; KLF6 is required for Alox5 induction by RUNX1-ETO9a, and KLF6 is specifically upregulated by RUNX1-ETO in human leukemia cells; loss of Alox5 reduces activity of RUNX1-ETO9a, MLL-AF9, and PML-RARα in vitro. ChIP assays; loss-of-function (shRNA/KO) in leukemia cell models; bone marrow transplantation assay; colony-forming assay PLoS genetics Medium 24130502
2014 Genetic deletion of ALOX5 in triple-transgenic Alzheimer's disease mice (3xTg/5LO-/-) prevents stress-induced tau hyperphosphorylation, increased GSK3β activity, long-term potentiation impairment, and fear-conditioned memory deficits caused by restraint/isolation stress, establishing that ALOX5 mediates stress-dependent propagation of Alzheimer's-like tauopathy. Genetic knockout (3xTg/5LO-/-); restraint/isolation stress paradigm; LTP electrophysiology; fear-conditioning behavior; Western blot for phospho-tau and GSK3β Human molecular genetics Medium 25122659
2015 Zebrafish ALOX2 is a functional ortholog of human ALOX5: it oxygenates arachidonic acid at the 5S position and also exhibits leukotriene synthase activity; triad determinant mutagenesis (Phe359Trp, Ala424Ile, Asn425Met) shifts reaction specificity from 5S- to dominant 15S-lipoxygenation, confirming that the same catalytic determinants govern positional specificity in both vertebrate orthologs. Recombinant expression in pro- and eukaryotic systems; HPLC product analysis; site-directed mutagenesis Biochimica et biophysica acta High 26456699
2016 JAK2V617F strongly upregulates Alox5 expression in hematopoietic cells; genetic deletion or pharmacological inhibition of Alox5 attenuates polycythemia vera (PV) development in mice by inducing cell-cycle arrest and apoptosis in PV cells and suppressing PV-initiating cells; mechanistically, Alox5 inhibition reduces AKT activation and decreases β-catenin expression in JAK2V617F-expressing cells. JAK2V617F PV mouse model; Alox5 knockout; zileuton pharmacological inhibition; colony formation from human JAK2V617F CD34+ cells; Western blot for AKT and β-catenin Cancer research High 27784744
2017 ALOX5 is transcriptionally repressed in MLL-rearranged AML via Polycomb repressive complex 2 (PRC2); restoration of Alox5 expression sensitizes MLL-rearranged leukemic cells to doxorubicin and cytarabine, with Stat and K-Ras signaling pathways negatively correlated with Alox5 overexpression. Affymetrix microarray; ChIP assay for PRC2; colony-forming and bone marrow transplantation assays; drug sensitivity assays in vitro and in vivo Scientific reports Medium 28500307
2017 Profilin 1 (PFN1) secreted by invasive extravillous trophoblasts induces decidualization of human endometrial stromal cells and downregulates ALOX5 expression in these stromal cells and in THP-1 macrophages, identifying a PFN1–ALOX5 signaling axis in decidualization during early pregnancy. Primary human endometrial stromal cell culture; recombinant PFN1 treatment; Western blot and qPCR for ALOX5; immunolocalization of ALOX5 in first-trimester decidua Scientific reports Medium 28821715
2019 Mutagenesis of the triad determinants (Phe359Trp/Ala424Ile/Asn425Met/Ala603Ile) in human ALOX5 abolishes its 5S-lipoxygenating and leukotriene synthase activity, instead producing 15(S)- and 8(S)-HpETE; structural docking, molecular dynamics, and QM/MM calculations confirm that these mutations alter substrate orientation within the active site cavity, linking pocket geometry to reaction specificity. Recombinant expression in Sf9 insect cells; HPLC product characterization; kinetic studies with stereospecifically deuterium-labeled substrates; in silico docking, MD simulation, QM/MM ACS chemical biology High 31664810
2020 Mass spectrometric DNA pulldown of the ALOX5 proximal promoter identified 66 specific binding proteins; key transcriptional regulators include known factors Sp1, Sp3, and Sp2, Krüppel-like factors KLF13 and KLF16, and zinc finger proteins MAZ, PRDM10, VEZF1, ZBTB7A, ZNF281, ZNF579; helicases BLM and DHX36, and hnRNPD/hnRNPK (G-quadruplex interactors) were also identified; spectroscopic and antibody methods confirmed that the GC-rich ALOX5 promoter forms DNA G-quadruplex structures that may regulate transcription. DNA pulldown coupled to label-free quantitative mass spectrometry; circular dichroism spectroscopy; antibody-based G-quadruplex detection The FEBS journal Medium 32096311
2020 LPS activates the ALOX5 promoter and increases 5-LO mRNA and protein expression in human monocytic cells (MM1, THP-1); LPS and TGF-β synergistically increase 5-LO product biosynthesis; LPS-driven ALOX5 promoter activation does not affect LTA4 metabolism, indicating LPS specifically upregulates early steps of leukotriene biosynthesis. ALOX5 promoter-luciferase reporter assay; RT-PCR and Western blot for 5-LO; HPLC-based 5-LO product measurement Prostaglandins, leukotrienes, and essential fatty acids Medium 32120263
2021 PKC-β overexpression drives BCR-ABL-independent TKI resistance in CML by upregulating Alox5 through ERK1/2 signaling; Alox5 in turn inactivates PTEN, sustaining TKI insensitivity; inhibition of PKC-β restores imatinib sensitivity in CD34+ CML cells and prolongs survival in a CML-PDX mouse model. shRNA knockdown; gene expression profiling (84-gene leukemia array); ERK1/2 pathway inhibitors; PTEN activity assays; in vivo PDX model with PKC-β inhibitor LY333531 Journal of cellular physiology Medium 33561320
2021 ALOX5 produces 5-HETE from arachidonic acid in gastric cancer cells; ALOX5 overexpression or exogenous 5-HETE activates MEK/ERK signaling to promote gastric cancer cell growth and reduce chemotherapy sensitivity, while ALOX5 inhibition suppresses ERK activation and sensitizes cells to chemotherapy. ALOX5 overexpression and pharmacological inhibition; phospho-ERK Western blot; cell growth and survival assays; 5-HETE ELISA Cancer medicine Medium 34121352
2022 Erk1-dependent phosphorylation of Alox5 targets it to the nuclear membrane where it mediates lipid peroxidation; resulting nuclear translocation of cytolytic molecules causes DNA damage and cell death independently of caspase-9; double knockout of caspase-9 and Alox5 in mice causes significant T cell expansion, demonstrating that these pathways function in parallel to regulate T cell death in vivo. Genome-wide siRNA library screen; caspase-9/Alox5 double-knockout mice; ROS and lipid peroxidation assays; subcellular fractionation/imaging; T cell proliferation/apoptosis assays Cells High 36231015
2022 LysOX promotes ferroptosis-associated lipid peroxidation in neurons via ERK-dependent activation of Alox5 (5-lipoxygenase) signaling; AAV-mediated LysOX overexpression enhances ferroptosis sensitivity and seizure-induced hippocampal damage, while pharmacological LysOX inhibition blocks seizure-induced Alox5-mediated ferroptosis. AAV-based LysOX overexpression in vivo; LysOX pharmacological inhibition (BAPN); ERK inhibitor studies; lipid peroxidation assays; seizure mouse model Acta pharmaceutica Sinica. B Medium 36176900
2023 HTTQ94 (polyglutamine-expanded N-terminal huntingtin fragment) activates ALOX5-mediated ferroptosis by stabilizing FLAP (5-LO activating protein), an essential cofactor of ALOX5 lipoxygenase activity; ALOX5 is required for HTTQ94-induced ferroptosis in response to ROS stress and glutamate, but is dispensable for common ferroptosis inducers (e.g., erastin); Alox5 genetic inactivation ameliorates HD pathology and extends lifespan in HD mice. RNAi-mediated genome screen; ALOX5 and FLAP co-immunoprecipitation/stabilization assays; neuronal cell ferroptosis assays; Alox5 knockout in HD mice; behavioral and pathological phenotyping Genes & development High 36921996
2023 ALOX5 promotes macrophage M2 polarization via the JAK/STAT pathway; lentiviral ALOX5 overexpression in macrophages induces M2-like phenotype and promotes chemotaxis toward pancreatic cancer cells; zileuton inhibits these effects by blocking ALOX5, reducing tumor invasion and liver metastasis in an orthotopic pancreatic cancer mouse model. Lentiviral ALOX5 overexpression; JAK/STAT pathway inhibitors; in vitro macrophage polarization assays; orthotopic nude mouse model; survival analysis International immunopharmacology Medium 37348233
2023 ALOX5 deficiency in bladder cancer cells permits ferroptosis escape; EGR1 transcriptionally regulates ALOX5 expression; CRISPR/Cas9 and RNAi loss-of-function confirmed that ALOX5 is required for ferroptosis sensitivity, with ALOX5-deficient high-pathological-stage bladder cancer cells showing ferroptosis resistance. CRISPR/Cas9 knockout; RNAi knockdown; RNA-seq; ferroptosis assays (lipid peroxidation, cell death); ChIP/reporter assays for EGR1-ALOX5 transcriptional regulation Cell death & disease Medium 38062004
2023 In intrahepatic cholangiocarcinoma, ALOX5-derived LTB4 binds BLT1/BLT2 receptors on tumor-associated macrophages (TAMs) and activates the PI3K pathway to promote M2 macrophage migration toward tumor cells; co-culture and bulk-sequencing confirmed PI3K as the key downstream pathway; combined ALOX5 inhibitor (zileuton) and CSF1R inhibitor reduced tumor volume and M2 macrophage infiltration in a xenograft model. In vitro macrophage co-culture model; LTB4 ELISA; BLT1/BLT2 receptor blocking; PI3K pathway inhibitors; bulk RNA-seq after co-culture; xenograft nude mouse model Journal of translational medicine Medium 38124204
2023 ALOX5 promotes autophagy-dependent ferroptosis in melanoma by activating the AMPK/mTOR pathway and inhibiting GPX4 expression; inhibition of autophagy reduces ALOX5-enhanced ferroptosis, indicating that ALOX5 and autophagy are synergistic; recombinant human ALOX5 protein exerts antitumor ferroptotic effects in a xenograft model. ALOX5 overexpression in melanoma cell lines and xenograft; AMPK/mTOR pathway analysis by Western blot; autophagy inhibitors; GPX4 expression; MDA/GSH/iron assays Biochemical pharmacology Medium 37080437
2024 ALOX5 activity in RA CD4+ T cells increases LTB4 production; LTB4 stimulates Ca2+ influx through ORAI3 channels, leading to NLRP3 inflammasome activation and pyroptosis; ALOX5 knockdown or pharmacological inhibition suppresses CD4+ T cell pyroptosis and improves symptoms in two rodent RA models. ALOX5 mRNA/protein quantification in patient T cells; ALOX5 knockdown; LTB4 ELISA; Ca2+ flux assays; ORAI3 blocking; NLRP3 inflammasome activation assays; rodent RA models Science signaling High 38412254
2024 In lung cancer-educated neutrophils, PARP-1 interacts with and PARylates (post-translationally modifies) ALOX5, stabilizing ALOX5 protein; this stabilization increases MMP-9 expression and promotes lung cancer cell invasion and tumor growth in vivo; PARP-1 knockdown or inhibition (AG14361) decreases ALOX5 expression and MMP-9 production, eliminating neutrophil-mediated cancer promotion. Co-immunoprecipitation; immunoprecipitation coupled to mass spectrometry (IP/MS); PARylation assay; gene knockdown; gelatin zymography for MMP-9; murine tumor model Cancer biology & medicine Medium 38172525
2024 ALOX5-derived 5-HETE from glioma cells promotes M2 polarization, PD-L1 expression, and migration of glioma-associated microglia/macrophages (GAMs) by facilitating nuclear translocation of NRF2; an anti-ALOX5 nanobody suppresses 5-HETE efflux, attenuates M2 GAM polarization, and reduces glioma progression; combination with anti-PD-1 shows superior anti-tumor efficacy. UHPLC-MS/MS oxylipin profiling; in vivo orthotopic glioma model with bioluminescence imaging; flow cytometry; immunofluorescence; NRF2 nuclear translocation assay; ALOX5-targeted nanobody; anti-PD-1 combination therapy Journal for immunotherapy of cancer Medium 39142719
2007 5-LOX is expressed in both resting peripheral blood T lymphocytes and T lymphoblastoid cell lines at the mRNA and protein level; the enzyme localizes primarily to the cytoplasm with some nuclear localization and translocates to the nuclear periphery following mitogenic stimulation; Jurkat cells, but not resting primary T cells, produce LTC4 and LTB4 upon CD3/CD28 cross-linking, and this synthesis is abolished by MK-886 and AA-861 (5-LO inhibitors), demonstrating stimulus-dependent translocation-linked enzymatic activation. RT-PCR; in situ RT-PCR; Western blot; immunofluorescence; FACS; LTC4/LTB4 synthesis assay with pharmacological inhibitors Immunology Medium 17484769
2000 5-LOX mRNA and protein are increased in hippocampus and cerebellum of aging rats, and the membrane/cytosol ratio of 5-LOX protein is larger in older versus younger brains, indicating that aging drives both increased ALOX5 expression and translocation/activation of the enzyme to membranes. Quantitative RT-PCR with internal standards; quantitative Western blotting; subcellular fractionation Neurobiology of aging Medium 11016533

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature genetics 394 10369259
2009 Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nature genetics 249 19503090
2005 Dual inhibition of 5-LOX and COX-2 suppresses colon cancer formation promoted by cigarette smoke. Carcinogenesis 129 15637091
2018 Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: A structure-based approach. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 114 29883727
2021 A novel mechanism linking ferroptosis and endoplasmic reticulum stress via the circPtpn14/miR-351-5p/5-LOX signaling in melatonin-mediated treatment of traumatic brain injury. Free radical biology & medicine 92 34883251
2004 New COX-2/5-LOX inhibitors: apoptosis-inducing agents potentially useful in prostate cancer chemotherapy. Journal of medicinal chemistry 87 15566290
2007 Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade. Carcinogenesis 84 18033773
2002 The mechanism of action of the new antiinflammatory compound ML3000: inhibition of 5-LOX and COX-1/2. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 83 12005204
2023 ALOX5-mediated ferroptosis acts as a distinct cell death pathway upon oxidative stress in Huntington's disease. Genes & development 81 36921996
2011 Psoralidin, a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation. Biochemical pharmacology 79 21669192
2008 ALOX5 variants associated with susceptibility to human pulmonary tuberculosis. Human molecular genetics 77 18174194
2018 1,2,3-triazole tethered Indole-3-glyoxamide derivatives as multiple inhibitors of 5-LOX, COX-2 & tubulin: Their anti-proliferative & anti-inflammatory activity. Bioorganic chemistry 59 30081353
2018 Frontline Science: Reprogramming COX-2, 5-LOX, and CYP4A-mediated arachidonic acid metabolism in macrophages by salidroside alleviates gouty arthritis. Journal of leukocyte biology 56 30265377
2011 Chemoprevention of colon and small intestinal tumorigenesis in APC(Min/+) mice by licofelone, a novel dual 5-LOX/COX inhibitor: potential implications for human colon cancer prevention. Cancer prevention research (Philadelphia, Pa.) 56 21885812
2017 MiR-216a-3p inhibits colorectal cancer cell proliferation through direct targeting COX-2 and ALOX5. Journal of cellular biochemistry 55 28786533
2013 Cannabinoid receptor 2 suppresses leukocyte inflammatory migration by modulating the JNK/c-Jun/Alox5 pathway. The Journal of biological chemistry 55 23539630
2018 Inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate crystal-induced inflammation. Toxicology and applied pharmacology 54 29763636
2006 ALOX5 promoter genotype, asthma severity and LTC production by eosinophils. Allergy 54 16364163
2023 The ALOX5 inhibitor Zileuton regulates tumor-associated macrophage M2 polarization by JAK/STAT and inhibits pancreatic cancer invasion and metastasis. International immunopharmacology 52 37348233
2008 ALOX5 promoter genotype and response to montelukast in moderate persistent asthma. Respiratory medicine 51 18339529
2009 The Alox5 gene is a novel therapeutic target in cancer stem cells of chronic myeloid leukemia. Cell cycle (Georgetown, Tex.) 50 19823023
2018 mPGES-1 and ALOX5/-15 in tumor-associated macrophages. Cancer metastasis reviews 48 29808459
2017 Pyrazole-hydrazone derivatives as anti-inflammatory agents: Design, synthesis, biological evaluation, COX-1,2/5-LOX inhibition and docking study. Bioorganic chemistry 48 28865292
2008 Common polymorphisms of ALOX5 and ALOX5AP and risk of coronary artery disease. Human genetics 48 18369664
2008 Identification of ALOX5 as a gene regulating adiposity and pancreatic function. Diabetologia 48 18421434
2000 Inflammatory 5-LOX mRNA and protein are increased in brain of aging rats. Neurobiology of aging 47 11016533
2024 Elucidating the role of tumor-associated ALOX5+ mast cells with transformative function in cervical cancer progression via single-cell RNA sequencing. Frontiers in immunology 46 39224598
2023 ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape. Cell death & disease 46 38062004
2003 Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 46 12911785
2015 Dual inhibition of COX-2/5-LOX blocks colon cancer proliferation, migration and invasion in vitro. Oncology reports 45 26707712
2023 ALOX5 promotes autophagy-dependent ferroptosis by activating the AMPK/mTOR pathway in melanoma. Biochemical pharmacology 44 37080437
2017 Effects of COX1-2/5-LOX blockade in Alzheimer transgenic 3xTg-AD mice. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 44 28238167
2007 COX-2/5-LOX dual acting anti-inflammatory drugs in cancer chemotherapy. Current topics in medicinal chemistry 42 17305571
2021 Synthetically-tailored and nature-derived dual COX-2/5-LOX inhibitors: Structural aspects and SAR. European journal of medicinal chemistry 38 34479036
2022 Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications. Acta pharmaceutica Sinica. B 36 36176900
2005 5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in vascular pathology and Alzheimer's disease. Medical hypotheses 36 16278051
2005 Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population. Journal of Korean medical science 36 16361798
2021 ALOX5-5-HETE promotes gastric cancer growth and alleviates chemotherapy toxicity via MEK/ERK activation. Cancer medicine 35 34121352
2017 ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged leukemia. Scientific reports 34 28500307
2015 Simultaneous targeting of 5-LOX-COX and EGFR blocks progression of pancreatic ductal adenocarcinoma. Oncotarget 33 26429877
2014 Absence of ALOX5 gene prevents stress-induced memory deficits, synaptic dysfunction and tauopathy in a mouse model of Alzheimer's disease. Human molecular genetics 33 25122659
2012 Evaluation of Cissus quadrangularis extracts as an inhibitor of COX, 5-LOX, and proinflammatory mediators. Journal of ethnopharmacology 33 22484053
2013 ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 31 23600541
2021 Licofelone, a potent COX/5-LOX inhibitor and a novel option for treatment of neurological disorders. Prostaglandins & other lipid mediators 29 34517113
2020 Conjugated linoleic acid attenuates 2,4-dinitrofluorobenzene-induced atopic dermatitis in mice through dual inhibition of COX-2/5-LOX and TLR4/NF-κB signaling. The Journal of nutritional biochemistry 29 32330842
2011 ALOX5 gene variants affect eicosanoid production and response to fish oil supplementation. Journal of lipid research 29 21296957
2024 ALOX5 drives the pyroptosis of CD4+ T cells and tissue inflammation in rheumatoid arthritis. Science signaling 28 38412254
2021 LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals With Diabetes. Diabetes 28 34417262
2018 Evaluation of the oxidative stress-related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population. Diabetes & vascular disease research 28 29383971
2016 Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index. Journal of the neurological sciences 28 26944113
2015 Structure Based Library Design (SBLD) for new 1,4-dihydropyrimidine scaffold as simultaneous COX-1/COX-2 and 5-LOX inhibitors. Bioorganic & medicinal chemistry 28 26122769
2007 Inhibitory activities and attenuated expressions of 5-LOX with red ginseng in Helicobacter pylori-infected gastric epithelial cells. Digestive diseases and sciences 28 17333352
2007 Expression of 5-lipoxygenase (5-LOX) in T lymphocytes. Immunology 28 17484769
2012 Conversion of pro-inflammatory murine Alox5 into an anti-inflammatory 15S-lipoxygenating enzyme by multiple mutations of sequence determinants. Archives of biochemistry and biophysics 27 23246375
2009 Convergence of the 5-LOX and COX-2 pathways: heme-catalyzed cleavage of the 5S-HETE-derived di-endoperoxide into aldehyde fragments. Journal of lipid research 27 19553698
2011 Enhancing antitumor effects in pancreatic cancer cells by combined use of COX-2 and 5-LOX inhibitors. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 21993002
2008 Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors. Prostaglandins, leukotrienes, and essential fatty acids 26 18280718
2020 Acetyl-11-keto-β-boswellic acid prevents testicular torsion/detorsion injury in rats by modulating 5-LOX/LTB4 and p38-MAPK/JNK/Bax/Caspase-3 pathways. Life sciences 25 32971106
2020 Aberrant ALOX5 Activation Correlates with HER2 Status and Mediates Breast Cancer Biological Activities through Multiple Mechanisms. BioMed research international 25 33224971
2017 Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5. Scientific reports 25 28821715
2010 Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors. Bioorganic & medicinal chemistry 25 20667741
2023 Caffeic acid modulates activation of neutrophils and attenuates sepsis-induced organ injury by inhibiting 5-LOX/LTB4 pathway. International immunopharmacology 24 37913569
2018 Synthesis, anti-inflammatory screening, molecular docking, and COX-1,2/-5-LOX inhibition profile of some novel quinoline derivatives. Bioorganic chemistry 24 29602046
2013 Cooperation between RUNX1-ETO9a and novel transcriptional partner KLF6 in upregulation of Alox5 in acute myeloid leukemia. PLoS genetics 24 24130502
2013 The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades. Naunyn-Schmiedeberg's archives of pharmacology 23 23771412
2011 A novel positive feedback loop involving FASN/p-ERK1/2/5-LOX/LTB4/FASN sustains high growth of breast cancer cells. Acta pharmacologica Sinica 22 21643005
2008 5-LOX, 12-LOX and 15-LOX in immature forms of human leukemic blasts. Leukemia research 21 18561999
2023 ALOX5 acts as a key role in regulating the immune microenvironment in intrahepatic cholangiocarcinoma, recruiting tumor-associated macrophages through PI3K pathway. Journal of translational medicine 20 38124204
2021 PKC-β/Alox5 axis activation promotes Bcr-Abl-independent TKI-resistance in chronic myeloid leukemia. Journal of cellular physiology 20 33561320
2017 Genetic Variations of Oxidative Stress Related Genes ALOX5, ALOX5AP and MPO Modulate Ischemic Stroke Susceptibility Through Main Effects and Epistatic Interactions in a Chinese Population. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 29041000
2015 Variants in ALOX5, ALOX5AP and LTA4H are not associated with atherosclerotic plaque phenotypes: the Athero-Express Genomics Study. Atherosclerosis 20 25721704
2005 Licofelone, a novel 5-LOX/COX-inhibitor, attenuates leukocyte rolling and adhesion on endothelium under flow. Biochemical pharmacology 20 15894291
2018 5-Lipoxygenase (ALOX5): Genetic susceptibility to type 2 diabetes and vitamin D effects on monocytes. The Journal of steroid biochemistry and molecular biology 19 30521849
2015 The lipoxygenase pathway in zebrafish. Expression and characterization of zebrafish ALOX5 and comparison with its human ortholog. Biochimica et biophysica acta 19 26456699
2017 5-LOX in Alzheimer's Disease: Potential Serum Marker and In Vitro Evidences for Rescue of Neurotoxicity by Its Inhibitor YWCS. Molecular neurobiology 18 28451886
2011 A high-fat diet induces bone loss in mice lacking the Alox5 gene. Endocrinology 18 22128029
2024 ALOX5 contributes to glioma progression by promoting 5-HETE-mediated immunosuppressive M2 polarization and PD-L1 expression of glioma-associated microglia/macrophages. Journal for immunotherapy of cancer 17 39142719
2016 Copy number variation in ALOX5 and PTGER1 is associated with NSAIDs-induced urticaria and/or angioedema. Pharmacogenetics and genomics 17 26959713
2006 TagSNP evaluation for the association of 42 inflammation loci and vascular disease: evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects. Human genetics 17 17115186
2021 Knock-In Mice Expressing a 15-Lipoxygenating Alox5 Mutant Respond Differently to Experimental Inflammation Than Reported Alox5 Mice. Metabolites 16 34677413
2016 Simultaneous targeting of 5-LOX-COX and ODC block NNK-induced lung adenoma progression to adenocarcinoma in A/J mice. American journal of cancer research 16 27293987
2009 Cardioprotective effect of 5-lipoxygenase gene (ALOX5) silencing in ischemia-reperfusion. Acta biochimica Polonica 16 20011686
2022 Interference of ALOX5 alleviates inflammation and fibrosis in high glucose‑induced renal mesangial cells. Experimental and therapeutic medicine 15 36605525
2020 Analysis of proximal ALOX5 promoter binding proteins by quantitative proteomics. The FEBS journal 15 32096311
2020 LPS induces ALOX5 promoter activation and 5-lipoxygenase expression in human monocytic cells. Prostaglandins, leukotrienes, and essential fatty acids 15 32120263
2016 Virtual Dual inhibition of COX-2 / 5-LOX enzymes based on binding properties of alpha-amyrins, the anti-inflammatory compound as a promising anti-cancer drug. EXCLI journal 15 27231478
2024 Cancer-educated neutrophils promote lung cancer progression via PARP-1-ALOX5-mediated MMP-9 expression. Cancer biology & medicine 14 38172525
2023 Exosomes derived from human adipose-derived stem cells alleviate hepatic ischemia-reperfusion (I/R) injury through the miR-183/ALOX5 axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 36786721
2021 Polyphenolic Profile of Callistemon viminalis Aerial Parts: Antioxidant, Anticancer and In Silico 5-LOX Inhibitory Evaluations. Molecules (Basel, Switzerland) 14 33923148
2020 CaMKIIγ regulates the viability and self-renewal of acute myeloid leukaemia stem-like cells by the Alox5/NF-κB pathway. International journal of laboratory hematology 14 33369192
2019 Mutations of Triad Determinants Changes the Substrate Alignment at the Catalytic Center of Human ALOX5. ACS chemical biology 14 31664810
2024 Magnolin alleviated DSS-induced colitis by inhibiting ALOX5-mediated ferroptosis. The Kaohsiung journal of medical sciences 13 38340032
2020 Effects of ALOX5, IL6R and SFTPD gene polymorphisms on the risk of lung cancer: A case-control study in China. International immunopharmacology 13 31918059
2012 Association of Sp1 tandem repeat polymorphism of ALOX5 with coronary artery disease in Indian subjects. Clinical and translational science 13 23067353
2024 Multiomics integrated analysis and experimental validation identify TLR4 and ALOX5 as oxidative stress-related biomarkers in intracranial aneurysms. Journal of neuroinflammation 12 39278904
2023 Hederagenin protects against myocardial ischemia-reperfusion injury via attenuating ALOX5-mediated ferroptosis. Naunyn-Schmiedeberg's archives of pharmacology 12 37955689
2022 Mitochondrion-Mediated Cell Death through Erk1-Alox5 Independent of Caspase-9 Signaling. Cells 12 36231015
2016 Alox5 Blockade Eradicates JAK2V617F-Induced Polycythemia Vera in Mice. Cancer research 12 27784744
2014 Low leukotriene B4 receptor 1 leads to ALOX5 downregulation at diagnosis of chronic myeloid leukemia. Haematologica 12 25193960
2024 Quercetin Alleviates LPS-Stimulated Myocardial Injury through Regulating ALOX5/PI3K/AKT Pathway in Sepsis. Cardiovascular toxicology 11 39068603